End-stage Renal Disease Of Unknown Etiology Research Articles

Comorbid Conditions in Kidney Transplantation: Outcome Analysis at King Abdulaziz Medical City.

Kidney transplantation is most commonly performed for end-stage renal disease (ESRD) and provides the best chance for a cure. The surgery is shown to be beneficial to a patient's quality of life after transplantation in multiple studies. But graft failure is a serious consequence that might happen. The term graft failure refers to the failure of a transplanted kidney to function properly. There are various reasons why this can happen, such as rejection, infection, or medication complications. A retrospective cohort study of comorbid conditions in patients who underwent renal transplantation at King Abdulaziz Medical City (KAMC) between 2016 and 2022.Data were collected by chart review using the BestCare system. The data collected included patients' demographics, comorbidities, calculated Charlson Comorbidity Index (CCI), surgery-related data, laboratory data, and the outcome of transplantation. The categorical data were presented using percentages and frequencies, while the numerical data were presented as mean and standard deviation. The Chi-square test was used for inferential statistics to find the association between categorical variables. A total of 669 patients were included in the current study. Of these, 422 (63.1%) were men, and the mean age was 44years. The incidence of graft failure within one year at KAMC was found to be 1.2% (eight cases). Regarding theCCIand its association with graft failure within one year, 37 (5.5%) patients had a myocardial infarction (MI) and 17 (2.5%) had congestive heart failure; however, no patients with MI or congestive heart failure experienced graft failure, and no significant association was found between MI or congestive heart failure and graft failure (p-value = 1.000 for both). A total of 417 (62.3%) patients had no or diet-controlled diabetes, 122 (18.2%) had uncomplicated diabetes mellitus (DM), and 130 (19.4%) had end-organ damage. DM and graft failure were not significantly associated (p-value = 1.000). A total of 286 (42.8%) patients had ESRD of unknown etiology, 109 (16.3%) patients had ESRD caused by diabetic nephropathy, and 100 (14.9%) had ESRD resulting from hypertension, apart from other causes. Most patients were found to have ESRD of unknown etiology and the most frequently reported known risk factor for ESRD and subsequent transplantation was found to be diabetic nephropathy, followed by hypertension.

#5782 AN EXCEPTIONAL CASE OF A PATIENT WITH TWO RARE GENETIC VARIANTS OF AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE AND ALPORT SYNDROME

Abstract Background Alport syndrome and autosomal dominant polycystic kidney disease (ADPKD) belong to the most prevalent monogenic causes of chronic kidney disease (CKD) and both progress to end stage renal disease (ESRD). Alport syndrome, is caused by mutations in genes encoding collagen IV protein family. Inheritance might be X-linked, autosomal recessive, autosomal dominant or digenic and several pathogenic variants have been identified. ADPKD is mostly caused by mutations in PKD1and PKD2 genes but recently, the GANAB gene, that encodes the glucosidase IIa subunit, has been identified has a cause of a milder form of ADPKD. We present a case report of a patients with CKD-4, bilateral sensorineural hearing loss and multiple renal cysts where two unrelated and distinct genetic variants of both diseases were concomitantly found. Case report A 63-year-old caucasian male with medical history of arterial hypertension, hematuria and bilateral sensorineural hearing loss since his 40 years-old, with cochlear implant surgery 13 years ago was referred to the Nephrology unit due to progressive CKD, currently stage 4. His mother had ESRD of unknown etiology, in peritoneal dialysis since the age of 78 years and he has two healthy sons (aged 16 and 20 years old). Physical examination was irremarkable. Laboratorial workout showed serum creatinine of 2.7 mg/dL, ratio albumin/creatinine of 105mg/g with 11 erythrocytes in urinary sediment. Renal ultrasound showed normal sized kidneys with more than 10 cysts in each kidney, the biggest with 44mm. Genetic testing via next generation sequencing was performed revealing heterozygous mutations in COL4A3 (c.4421T>C p.(Leu1474Pro)), reported in ClinVar, and described in literature as an autosomal dominant variant present in Alport families. A mutation in the GANAB (c.2281A>G p.(Thr761Ala)) gene, classified as variants of unknown significance in was also detected, but this mutations is not reported in gnomAD or ClinVar. The patient was referred for genetic counseling. Conclusion We describe a rare case of possible overlap of ADPKD and Alport syndrome. The COL4A3 mutation is described has having a risk ≥ 20% of developing ESRD, but the association of a mild variant of ADPKD might increase exponentially this risk.

An accessible insight into genetic findings for transplantation recipients with suspected genetic kidney disease

Determining the etiology of end-stage renal disease (ESRD) constitutes a great challenge in the context of renal transplantation. Evidence is lacking on the genetic findings for adult renal transplant recipients through exome sequencing (ES). Adult patients on kidney transplant waitlist were recruited from 2017 to 2019. Trio-ES was conducted for the families who had multiple affected individuals with nephropathy or clinical suspicion of a genetic kidney disease owing to early onset or extrarenal features. Pathogenic variants were confirmed in 62 from 115 families post sequencing for 421 individuals including 195 health family members as potential living donors. Seventeen distinct genetic disorders were identified confirming the priori diagnosis in 33 (28.7%) families, modified or reclassified the clinical diagnosis in 27 (23.5%) families, and established a diagnosis in two families with ESRD of unknown etiology. In 14.8% of the families, we detected promising variants of uncertain significance in candidate genes associated with renal development or renal disease. Furthermore, we reported the secondary findings of oncogenes in 4.4% of the patients and known single-nucleotide polymorphisms associated with pharmacokinetics in our cohort to predict the drug levels of tacrolimus and mycophenolate. The diagnostic utility of the genetic findings has provided new clinical insight in most families that help with preplanned renal transplantation.

Mutational screening of inverted formin 2 in adult-onset focal segmental glomerulosclerosis or minimal change patients from the Czech Republic

BackgroundMutations in INF2 are frequently responsible for focal segmental glomerulosclerosis (FSGS), which is a common cause of end stage renal disease (ESRD); additionally, they are also connected with Charcot-Marie-Tooth neuropathy. INF2 encodes for inverted formin 2. This protein participates in regulation of the dynamics of the actin cytoskeleton, involving not only the polymerisation, but also the depolymerisation of filaments. The present study is the first mutational analysis of INF2 done in the Czech Republic.MethodsMutational analysis of INF2 was performed on 109 patients (mean age at onset 41.44 ± 18.91 years) with FSGS or minimal change disease (MCD); and also in 6 patients without renal biopsy who had already developed chronic kidney disease (CKD)/ESRD at the time of diagnosis. We used high resolution melting method (HRM), with subsequent Sanger sequencing, in suspect samples from HRM analysis. The HRM method is an effective method for the screening of large cohorts of patients.ResultsTwo pathogenic mutations (p.Arg214His and p.Arg218Gln) were detected in INF2. The first (p.Arg214His) was identified in the FSGS patient with a positive family history. The second mutation (p.Arg218Gln) was found in two brothers with ESRD of unknown etiology. The most frequent sequence change was the substitution p.P35P, the incidence of which corresponded with the frequencies available in the ExAC Browser and gnomAD Browser databases. This analysis also detected different exonic and intronic changes that probably did not influence the phenotype of the included patients.ConclusionsThe INF2 mutational screening is useful in familial FSGS cases as well as in patients with an unknown cause for their ESRD, but with a positive family history. INF2 seems to be not only the cause of FSGS, but also of ESRD of unknown etiology. Our study has confirmed that the HRM analysis is a very useful method for the identification of single nucleotide substitutions.

Current state of continuous ambulatory peritoneal dialysis in Egypt.

Patients with end-stage renal disease (ESRD) continue to increase in number worldwide, especially in developing countries. Although continuous ambulatory peritoneal dialysis (CAPD) has comparable survival advantages as hemodialysis (HD), it is greatly underutilized in many regions worldwide. The prevalence of use of CAPD in Egypt is 0.29/million population in 2017. The aim of this study is to describe the current state and practice of CAPD in Egypt and included 22 adult patients who were treated by CAPD. All the study patients were switched to CAPD after treatment with HD failed due to vascular access problems. Patients were mainly female (68.2 %) with the mean age of 49.77 ± 11.41 years. The average duration on CAPD was 1.76 ± 1.30 years. Hypertension was the main cause of end-stage renal disease (ESRD) constituting 36.4%, followed by diabetes (27.3 %), and toxic nephropathy (4.5%). Of importance is that about 31.8% of patients had ESRD of unknown etiology. The mean weekly Kt/V urea of patients on PD was 1.92 ± 0.18. The mean hemoglobin, serum calcium, phosphorus, parathormone, and albumin levels were 10.27 ± 1.98 g/dL, 8.36 ± 1.19 mg/dL, 5.70 ± 1.35 mg/dL, 541.18 ± 230.12 pg/mL, and 2.98 ± 0.73 g/dL, respectively. There was no significant difference between diabetic and nondiabetic CAPD patients regarding demographic and laboratory data. Our data indicate that there is continuing underutilization of CAPD in Egypt which may be related to nonavailability of CAPD fluid, patient factors (education and motivation), gradual decline of the efficiency of health-care professionals, and lack of a national program to start PD as the first modality for renal replacement therapy. It is advised to start an organized program to make CAPD widespread and encourage local production of PD fluids to reduce the cost of CAPD.

Screening of Fabry disease in patients with end-stage renal disease of unknown etiology: the first Thailand study.

We aimed to explore the prevalence of Fabry disease in Thai patients who were diagnosed with end-stage renal disease (ESRD) of an unknown origin. Venous blood samples were collected from ESRD patients for biochemical and molecular studies. Alpha-galactosidase A (α-GAL A) screening was performed from dried-blood spots using fluorometry. Molecular confirmation was performed using DNA sequencing of the GLA gene. A total of 142 male and female patients were included in this study. Ten patients (7.04%) exhibited a significant decrease in α-GAL A activity. There were no definitive pathogenic mutations observed in the molecular study. However, four patients revealed a novel nucleotide variant at c.1 -10 C>T, which was identified as a benign variant following screening in the normal population. In conclusion, the α-GAL A assay utilizing dried-blood spots revealed a significant false positive rate. There was no definitive Fabry disease confirmed in Thai patients diagnosed with ESRD of unknown etiology.